This project is designed to characterize the precursors of thymus-derived (T) lymphocytes in normal mouse bone marrow. A model has been developed in which the thymus, by means of a hormone, controls the maturation of precursors. This model, demonstrated in vivo, is being tested in a newly-developed in vitro cloning assay, whereby single precursors give rise to a colony in semi-solid medium. The growth characteristics and requirements will be determined, and then attempts will be made to induce immunological tolerance in these precursors. These studies should allow us to explore the mechanisms by which diversity is generated in developing T cells, and to test different models of self/non-self discrimination.